Common drug offers new hope for people with mood disorders

In a preliminary study, a team of researchers at Deakin University has found a promising new application for a drug used worldwide to treat high blood pressure.

Angiotensin Converting Enzyme Inhibitors, known as ACE inhibitors, appear to reduce the risk of mood disorders in the general population by over 80 per cent. If replicated by follow-up research, this finding could offer relief for thousands of people around the world for whom current treatments, such as antidepressants, are ineffective.

The research is being undertaken at Deakin’s Centre for Innovation in Mental and Physical Health and Clinical Treatment (IMPACT). NHMRC Career Development Fellow Dr Lana Williams and Alfred Deakin Postdoctoral Research Fellow Dr Brisa Fernandes and their colleagues are among the first in the world to investigate the potential of ACE inhibitors to treat mood disorders such as bipolar disorder and major depression.

“Mood disorders are characterised by a low grade inflammatory state,” said Dr Williams.

“As well as playing a pivotal role in regulating blood pressure, the renin-angiotensin hormone system is one of the pathways that modulates inflammation in the central nervous system. It appears to play a key role in regulating the stress response.”

To test their hypothesis, the team aimed to determine whether ACE inhibitors reduce the risk of mood disorders through a retrospective analysis of a sample group of 961 men, who have been participating in the population based, longitudinal Geelong Osteoporosis Study (GOS) since it was established in 1993.

They found that using ACE inhibitors to treat hypertension had the unexpected benefit of substantially preventing the onset of depression in the general population.

The drugs have been available since the 1980s and are generally safe to use, with few side effects.

Dr Fernandes explained that a key component of the renin-angiotensin system is the peptide angiotensin I, which is converted to angiotensin II by the angiotensin-converting enzyme in the kidneys and the brain.

“Angiotensin II exerts its actions in the brain through two different receptors, AT1 and AT2. AT1 is generally associated with increased oxidative stress and neurodegeneration, and AT2 is associated with neural growth,” she said.

“The AT2 receptor blockers block AT1, the receptor associated with neural degeneration. As well as helping people with mood disorders, it also appears to improve general cognition, so it could benefit people with other conditions such as Alzheimer’s disease.”

To progress their research on mood disorders, Dr Fernandes and her team hope to test the effectiveness of ACE inhibitors on larger samples of patients over the next few years. They have designed two clinical trials, which are currently being reviewed by the National Health and Medical Research Council.

If their early findings are replicated, ACE inhibitors could be used for patients with bipolar disorder and major depression. Since these drugs are already in the market, if the benefit is confirmed, they could be prescribed in the coming years.